Our proposed research is aimed: 1) at providing a mechanistic understanding of the kinetics of cholesterol gallstone dissolution in bile from the physical chemical standpoint, and 2) at developing thereby a rational approach to the medical therapy of the gallstone disease. Effort is being directed toward establishing correlations between physical models and in vitro experimental results with gallstones and with cholesterol monohydrate pellets and single crystals. Special emphasis is being directed toward the understanding of the recently discovered interfacial barrier which appears to rate-limit both the in vitro dissolution of gallstones and cholesterol monohydrate crystals in bile salt lecithin solutions. Efforts are being put into seeking out and studying conditions, procedures, and chemical agents that may, from a kinetic viewpoint, significantly accelerate cholesterol gallstone dissolution. Animal models are to be used in testing the in vitro findings with regard to safety and effectiveness. Eventual human tests are being planned to be carried out at the Mayo Clinic.